Currently, the first standard therapy for the permanent cure for cancer is chemical therapy, hormone therapy, or irradiation therapy, or combination thereof, but there has been a problem of occurrence of the side-effects. On the other hand, immune therapy has attracted attention as a promising therapy that avoids the side effects of traditional therapies. However, a characteristic of the immune therapy is mechanisms of action via cancer immunity of a patient, and therefore a large part of the therapy is yet unclear, its effects are different among individuals, and it is said that a relatively long term is required for treatment. In particular, in the case of a new medical agent that may require a relatively long period of treatment, it is very difficult to determine timing for evaluation of effectiveness for each of the patients, and in the case of adopting conventional timing to evaluate, even if the therapy can actually generate anti-tumor effects, its evaluation would be determined as no effect before confirming the effect. Therefore, in order to overcome the problem for the immune therapy, a method for detecting a pharmacological reaction before the timing to judge the effect, namely, a determination method capable of estimating the treatment effect has been required.
The anti-human PD-1 antibody is utilized as an anticancer and as an agent for fighting infectious diseases. It acts as an agent for enhancing cancer immunity by suppressing the immune suppression signal via PD-1, which is an immune suppression receptor (See US 2009/0217401, WO 03/011911, and WO 04/004771, incorporated herein by reference in their entirety.). However, a determination method capable of estimating the therapeutic effects has not been reported yet.
The present invention provides compositions and methods for detecting the efficacy of anti-human PD-1 antibody therapies and includes immunoglobulin(s), CD5L, gelsolin, and the like, which change in the blood, as biomarkers capable of estimating the therapeutic effects by the anti-human PD-1 antibody. For the immunoglobulins, in Nishimura et al., (and three persons), International Immunology, Vol. 10, No. 10, 1998, p. 1563-1572, it has been reported that the increase of serum IgG3, IgG2b, and IgA of the PD-1 deficient mouse is observed, and for gelsolin, in Yang et al., (and nine persons), BMC Cancer, Vol. 6, No. 203, 2006, p. 1-10, the relationship between expression amount of gelsolin and death risk has been reported, but the relationship between the gelsolin expression level and the anti-cancer effects by the anti-human PD-1 antibody has not been reported at all.